Search Results (398)

Colorectal cancer remains a leading cause of cancer-related mortality despite a prolonged and preventable precancerous phase. This review examines how artificial intelligence and emerging biomarkers may narrow the persistent gap between detecting established cancer and identifying advanced precursor lesions. Blood-based assays integrating cell-free DNA methylation, mutations, fragmentomic patterns, and other analytes achieve encouraging sensitivity for invasive colorectal cancer but remain substantially less sensitive for advanced adenomas and sessile serrated lesions, particularly in prospective average-risk populations. Machine-learning methods can integrate complementary molecular signals, although many models remain limited by case–control designs, spectrum bias, and inadequate external validation. Computer-aided detection increases adenoma detection and reduces miss rates, but benefits for advanced neoplasia, serrated lesions, colorectal cancer incidence, and mortality remain uncertain. AI-augmented digital pathology may improve polyp classification, dysplasia grading, invasive carcinoma recognition, and case prioritization after lesion removal. The greatest clinical value of these technologies is likely to arise from coordinated use within a multimodal, risk-adapted pathway that expands screening participation, prioritizes colonoscopy for individuals at greatest risk, and preserves high-quality colonoscopy and polypectomy as the central preventive intervention. Full article

Background/Objectives: Circular RNAs (circRNAs) are emerging regulators of genetic information that share the spliceosome biogenesis pathway with messenger RNAs (mRNAs), influencing their expression. There is an increasing body of evidence supporting their role in colorectal cancer (CRC) tumorigenesis. This study explored circRNAs in two distinct CRC tumorigenesis pathways: microsatellite instability (MSI) and microsatellite stability (MSS). We investigated competition between mRNA and circRNAs from their host genes, which could potentially disrupt normal gene regulation, and examined specific patterns of alterations in MSS and MSI tumors. Methods: Circular (circ) and linear (lin) exon–exon junctions were quantified using exon-specific probes targeting 48 genes involved in CRC predisposition and tumorigenesis processes. RNA was extracted from colorectal FFPE samples (stage 1 to 4 adenocarcinomas and adenomas). MSS tumors (MSS-TTs) and adjacent normal tissue (MSS-NT) were selected from 21 patients with a severe personal or family history of cancer. MSI tumors (MSI-TTs) and adjacent normal tissue (MSI-NT) were selected from 16 patients. Muscle content was also investigated as a potential confounding factor. Results: Principal component analysis distinguished NT from TT samples based on the sums of circular and linear junctions. CircRNA abundance was higher in samples with an elevated muscle content (Kruskal–Wallis test p-value = 0.034). Linear regression, adjusted for muscle content, showed significantly reduced global circRNA levels in tumors compared to in healthy tissues (MSI and MSS combined, p-value = 0.00268). In the MSS group, significant differences were observed between MSS-NT and MSS-TT in terms of circ/lin ratios and linear and circular junction counts for specific genes. MSI analysis revealed distinct gene profiles, with significant differences only in linear junction counts. Conclusions: Our results do not suggest competition between the circRNAs and mRNAs of the key oncogenic genes that we investigated, but they do reveal differences in circRNA/mRNA expression patterns within normal and tumor tissues. Full article

Colonoscopy is a key screening method for colorectal cancer (CRC), but its effectiveness is limited. Computer-aided detection (CADe) and computer-aided diagnostics (CADx), as part of an artificial intelligence (AI) system, improve the detection and optical characterization of lesions. This review maps and analyzes the evidence on the application of AI in colonoscopy, with a focus on the detection, segmentation, and characterization of colon neoplasms, available platforms, architectural models and implementation. The review was conducted in accordance with JBI and PRISMA-ScR guidelines, using the PCC framework. Meta-analyses, randomized controlled trials, systematic and narrative reviews, observational studies, guidelines, and consensus documents on the use of AI systems in different phases of colonoscopy were searched. CADe significantly improves adenoma detection and reduces the number of missed lesions. CADx, segmentation, depth of invasion assessment, and detection of learned lesions remain limited and heterogeneous. CADe has strong evidence for improving ADR, whereas current evidence for CADx remains insufficient to support a “resect-and-discard” strategy. Further cost-effectiveness studies are needed. Commercial platforms vary in their features and level of clinical validation. Colonoscopy using AI is a current topic with rapid development. This scoping review comprises heterogeneous literature covering clinical applications, technical aspects, the potential benefits and limitations of AI in improving colonoscopy performance and reducing the burden of colorectal cancer. Further trials involving diverse patient populations across different countries are needed to validate and extend the current evidence. Full article

Background/Objectives: Given the increasing burden of colorectal cancer (CRC), effective screening strategies are essential for early disease detection. As a primary endpoint, this study aimed for the assessment and comparison of two different diagnostic pathways in the Romanian population: population-based screening using the fecal immunochemical test (FIT) and opportunistic, symptom-driven, colonoscopy. Methods: A retrospective observational study was conducted in two groups comprising a total of 236 patients from an average-risk population across Romania. Group A consisted of patients diagnosed through a CRC screening pathway based on FIT, whereas group B included patients diagnosed following opportunistic colonoscopy performed in routine clinical practice. Patients were retrospectively analyzed according to the tumor–node–metastasis (TNM) classification, with early- versus late-stage disease defined on the basis of overall TNM stage. Overall stage, tumor (T) stage and lymph node (N) stage were additionally analyzed as ordinal outcomes. Binary and ordinal logistic regression models were adjusted for tumor location. Results: The odds of detecting CRC in stage I were 2.76-fold higher in the screening group than in the opportunistic colonoscopy group. For advanced stage disease, the difference did not show statistical significance. Analyses, stratified by tumor location, identified a statistically significant association for left-sided colon and rectal tumors. The odds of detecting a T1 tumor were 6.34-fold higher in the screening group than in the opportunistic colonoscopy group. Regarding lymph node involvement, the odds of detecting N0 disease were 2.03-fold higher in Group A than in Group B. Conclusions: Compared with opportunistic diagnosis, the screening pathway was associated with a higher likelihood of detecting CRC at an earlier stage, including tumors with limited local invasion and no lymph node involvement. These findings support the potential benefit of population-based CRC screening for earlier disease detection, although they should be interpreted in the context of the observational study design. Full article

Background: Colonoscopy is the gold-standard screening modality for colorectal cancer (CRC) prevention, enabling detection and endoscopic resection of premalignant polyps and reducing CRC incidence and mortality by up to 77% and 53%, respectively. However, colonoscopy effectiveness is substantially dependent on endoscopist expertise, with significant inter-operator variability in adenoma detection rates (ADR) and, consequently, a risk of missed lesions, particularly diminutive and morphologically subtle adenomas. Recent advances in artificial intelligence (AI), specifically computer-aided detection (CADe) and computer-aided diagnosis (CADx) systems utilizing deep learning convolutional neural networks, have emerged as promising technologies to standardize lesion detection accuracy and reduce adenoma miss rates. Methods: A focused narrative literature review was conducted examining randomized controlled trials, meta-analyses, and implementation studies evaluating AI-assisted colonoscopy systems across diverse clinical populations and healthcare settings. Results: Evidence demonstrates that CADe systems consistently improve ADR, particularly for diminutive polyps and morphologically challenging lesions, though superiority over expert endoscopists remains inconsistent. CADx systems reliably meet ASGE-PIVI performance thresholds for diminutive polyp characterization, supporting implementation of resect-and-discard and diagnose-and-leave strategies. However, substantial heterogeneity exists regarding real-world effectiveness, cost-effectiveness, and optimal implementation frameworks across diverse settings. Conclusions: While AI-assisted colonoscopy demonstrates clinical promise in improving lesion detection and enabling optical diagnosis, realizing durable population-level benefit requires the establishment of standardized validation methodologies, large-scale pragmatic trials with patient-centered outcomes, robust regulatory frameworks, and equitable implementation strategies addressing health disparities globally. Full article

Background/Objectives: Colonoscopy withdrawal time is an established quality indicator, but ongoing debate exists regarding whether its relationship with adenoma detection follows a fixed threshold or a continuous dose–response pattern. Methods: We retrospectively analyzed 31,780 colonoscopies from a multicenter endoscopy database to evaluate the relationship between withdrawal duration and lesion detection. Withdrawal time was assessed as both a continuous and categorical variable, and adenoma detection rate (ADR) and polyp detection rate (PDR) were examined across quartiles and clinically relevant intervals. Results: ADR increased progressively from 7.72% in the shortest withdrawal-time quartile to 36.47% in the longest quartile, while PDR increased from 21.22% to 67.86% (both p for trend <0.001). In the multivariable analysis adjusted for age, sex, and bowel-preparation quality, each additional minute of withdrawal time was independently associated with higher odds of adenoma detection (adjusted OR 1.14, 95% CI 1.13–1.15; p < 0.001). Although the confidence interval was narrow, reflecting the large sample size, the effect was clinically appreciable: model-predicted adenoma detection increased from 13.6% at six minutes to 21.0% at eight minutes and 28.2% at ten minutes, corresponding to approximately seven and fifteen additional adenoma-positive examinations per hundred procedures, respectively. The association remained consistent across age and sex strata. Receiver operating characteristic analysis showed moderate discrimination (area under the curve 0.701), with a Youden-optimal region of approximately 7 to 8 min. Because recorded withdrawal time incorporates interventional time, the principal analysis of inspection effort was conducted at the level of the endoscopist, using withdrawal time measured exclusively in the 14,611 examinations in which no polyp was detected and no tissue was sampled. Among 107 endoscopists contributing 26,793 procedures, inspection time was associated with adenoma detection (Spearman ρ = 0.46; p < 0.001), corresponding to an absolute increase of approximately 1.5 percentage points per additional minute, with attenuation of the gradient beyond approximately seven minutes. Conclusions: The procedure-level findings above describe the association with recorded withdrawal duration as captured in routine practice and are reported as supportive rather than as estimates of inspection effort. Together these analyses indicate that inspection time is associated with adenoma detection in a graded manner extending beyond the historical 6 min benchmark. Full article

Background/Objectives: Chemerin is an adipokine implicated in metabolic regulation, inflammation and cancer biology, but its value as a circulating biomarker in colorectal neoplasia remains uncertain. We investigated serum chemerin concentrations in patients with colorectal cancer (CRC), patients with colorectal polyps and colonoscopy-negative controls, and explored chemerin immunoreactivity in available polyp and tumour tissue. Methods: This exploratory observational case–control study included 41 patients with CRC, 20 patients with colorectal polyps and 29 colonoscopy-negative controls. Serum chemerin was measured by ELISA. Tissue specimens underwent routine histopathology and qualitative immunohistochemical staining for chemerin. Between-group comparisons were performed using non-parametric tests; subgroup analyses were exploratory and unadjusted. Results: Serum chemerin concentrations did not differ significantly between CRC and controls (median 144.0 vs. 135.7 ng/mL; p = 0.41), CRC and polyp groups (144.0 vs. 97.4 ng/mL; p = 0.24), or polyp and control groups (97.4 vs. 135.7 ng/mL; p = 0.94). Chemerin immunostaining was absent in CRC tissue (0/41) and conventional adenomatous polyps (0/15), whereas all available hyperplastic/serrated lesions showed epithelial cytoplasmic and/or stromal immunoreactivity (5/5); in lesions containing dysplasia, dysplastic glands showed no detectable staining. In controls, higher chemerin concentrations were associated with hyperglycaemia, hypertension, body weight and bilirubin, but these exploratory findings were not adjusted for multiplicity or metabolic confounding. Conclusions: In this exploratory cohort, serum chemerin did not discriminate CRC or colorectal adenoma from colonoscopy-negative controls. Together with the absence of staining in CRC and conventional adenomas, the findings argue against chemerin as a standalone circulating or commonly expressed tissue biomarker for these lesions under the assay conditions used. Immunoreactivity in the non-dysplastic epithelial and/or stromal compartments of hyperplastic/serrated lesions remains preliminary and requires prospective confirmation with standardised pre-analytics, quantitative pathology scoring and adjustment for metabolic confounders. Full article

Fusobacterium nucleatum has been implicated in colorectal cancer, but its role in adenomas remains unclear. We applied an RNA-based detection of F. nucleatum in formalin-fixed paraffin-embedded adenoma tissue and explored the mutational landscape and transcriptomic profile of F. nucleatum+ patients in comparison to F. nucleatum- patients. Bespoke F. nucleatum probes successfully detected F. nucleatum in 11% of adenomas. F. nucleatum+ patients exhibited a positively enriched anti-bacterial defence response and immune-related transcriptomic signatures, as well as a proliferative profile. These findings suggest that F. nucleatum positivity is associated with immune and proliferative transcriptomic signatures in colorectal adenomas, but this requires validation in larger, longitudinal cohorts. Full article

Since the discovery of truncated mutations of adenomatous polyposis coli proteins in familial adenoma patients in 1991, the mechanism of cytosolic β-catenin regulation has been intensively studied, and now it is very well known that the central role of the canonical Wnt/β-catenin is in colorectal cancer. However, Wnt signaling is very complicated because of the presence of almost 20 Wnt ligand genes, six Frizzled seven-transmembrane receptors, and three LRP co-receptors. In addition, research in the past two decades illuminated the existence of the other Wnt signaling—non-canonical Wnt signaling (Wnt/PCP and Wnt/Ca²⁺ pathways), and an increasing number of studies have shown the potential role of non-canonical Wnt signaling in cancer recently. One of the well-studied Wnt ligands in non-canonical Wnt signaling is Wnt-5a. However, the role of Wnt-5a and non-canonical pathways in cancer is mosaic—i.e., it may involve tumor-promoting or suppressing pathways. In certain cancers, non-canonical Wnt signaling may mainly act as a tumor promoter, yet the results are very controversial in colorectal cancer. Elucidating the role of non-canonical Wnt signaling in colorectal cancer may be very important to further reduce the risk of colorectal cancer, especially in patients who do not carry truncated mutations of adenomatous polyposis coli. In this review, I would like to mainly discuss the apparent controversy surrounding non-canonical Wnt signaling in colorectal cancer, and I would like to point out a few potential reasons contributing to the mysterious roles of Wnt5a-initiated non-canonical signaling in colorectal cancer. Full article

Background: Colorectal neoplasia in adults younger than 50 years has attracted increasing clinical attention because of the rising incidence of early-onset colorectal cancer. However, the clinicopathological characteristics of colorectal lesions detected in younger adults remain incompletely described. This study aimed to characterize the clinical, anatomical, and histopathological features of colorectal neoplasia in adults younger than 50 years undergoing colonoscopy. Methods: This retrospective single-center study included adults aged 18–49 years who underwent complete colonoscopy between January 2018 and December 2023. After exclusion of individuals with normal colonoscopy findings, 152 patients with at least one colorectal lesion were included. Lesions were classified as benign, advanced, or malignant according to established histopathological criteria. Demographic, endoscopic, and pathological characteristics were analyzed and compared across lesion categories. Results: Among 152 patients, 83 (54.6%) had benign lesions, 64 (42.1%) had advanced neoplasia, and 5 (3.3%) had malignant lesions. Advanced lesions were observed predominantly in individuals aged 40–49 years. Most lesions were detected in symptomatic patients undergoing clinically indicated colonoscopy. Histopathological evaluation demonstrated a higher frequency of villous/tubulovillous adenomas, sessile serrated lesions, and high-grade dysplasia among advanced lesions. Larger lesion size was strongly associated with advanced pathological features (p < 0.001). In multivariable analysis, patients aged 30–39 years had significantly lower odds of advanced or malignant neoplasia than those aged 40–49 years, whereas no independent associations were observed for sex, smoking status, alcohol use, family history of colorectal cancer, or lesion location. Conclusions: In this selected cohort of adults younger than 50 years with detected colorectal lesions undergoing clinically indicated colonoscopy, advanced neoplasia represented a substantial proportion of cases. These findings should not be extrapolated to the general population of adults younger than 50 years or to screening cohorts. Full article

Early detection of colorectal cancer (CRC) is a major determinant of patient prognosis, as survival strongly depends on disease stage at diagnosis. Despite advances in screening programs, a significant proportion of CRC cases are still diagnosed at advanced stages, underscoring the need for improved early detection strategies. Most sporadic CRCs arise through the adenoma–carcinoma sequence over 10 to 15 years, providing a window for the detection of premalignant lesions, such as advanced adenomas. Current screening approaches are based on colonoscopy or its combination with stool-based tests. Although colonoscopy is the gold standard, it is an invasive technique with high associated costs and limited patient compliance. Stool-based tests are non-invasive and more widely accepted but lack specificity and sufficient sensitivity for detecting premalignant lesions. In this context, liquid biopsies have emerged as a promising minimally invasive alternative for identifying tumor-derived biomarkers in biological fluids such as blood or stool. Small non-coding RNAs (sncRNAs), and particularly microRNAs (miRNAs), have gained considerable attention as non-invasive biomarkers for their highly stability, resistance to handling conditions, and reliable quantification even in low-input samples. Single miRNAs and miRNA signatures detected in biofluids and combined with clinical parameters have shown promise for CRC detection. However, their utility for detecting advanced adenomas remains insufficiently characterized. Further validation in large, independent cohorts and standardization of analytical methods are required before their clinical implementation. Despite these challenges, sncRNA-based liquid biopsies represent a promising approach for improving early detection of CRC and, consequently, its prognosis. Full article

Intratumor heterogeneity (ITH) of premalignant colorectal lesions is an important area of research for understanding the diverse biological behavior of colorectal cancer (CRC). Accurate assessment of ITH depends substantially on the sampling strategy used. We present a novel methodological approach termed whole tumor heterogeneity topography (WTHT) and compare it with three previously described sampling strategies: whole tumor homogenization, macrodissection of selected tumor regions, and multisampling. A cohort of 184 advanced precancerous colorectal lesions was processed into paraffin blocks, and the entire tumor mass was systematically divided into equally sized samples (~10 mm³). DNA was isolated from each sample separately and analyzed for hotspot mutations in APC, KRAS, BRAF, PIK3CA, and TP53. ITH was quantified using mutation variance and a newly introduced Heterogeneity Grade (HG). Results obtained by WTHT were statistically and graphically compared with three other modeled sampling strategies. Significant differences were observed among the analyzed sampling approaches. Macrodissection showed the greatest deviation from WTHT, indicating substantial sampling bias, whereas multisampling produced the closest results. WTHT enabled precise quantification and spatial mapping of mutational clones across the entire lesion. WTHT combined with HG provides a robust and reproducible framework for comprehensive assessment of ITH in colorectal adenomas. Full article

Background/Objectives: Early-onset colorectal cancer (EO-CRC) incidence continues to rise globally, yet age-stratified risk data for adults under 45 remain limited. Methods: This retrospective, single-center, colonoscopy-based cohort study included 3959 examinees aged 18–44 at Peking University International Hospital (2023–2024) and used Joinpoint regression to identify age inflection points for polyp detection rates. Case–control analysis with Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression assessed metabolic risk factors for adenoma and serrated polyps in the 40–44 stratum. Results: Detection rates for polyps, adenomas, and serrated lesions all rose with age (p < 0.001). From the youngest (18–29) to the oldest (40–44) group, the polyp detection rate increased 2.6-fold, the adenoma detection rate (ADR) 4.3-fold, and the serrated lesion detection rate 2.0-fold. Joinpoint regression revealed an ADR inflection at age 33 (annual percentage change (APC): +0.51% → +1.27%), a high-risk adenoma (HRA) inflection at age 39 (APC: +0.14% → +0.77%), and an advanced-neoplasia inflection also at age 39 (APC: +0.20% → +0.81%). Across age strata, adenoma and advanced-neoplasia detection rates were comparable between asymptomatic screening and symptomatic examinees from age 35 onward (40–44 ADR 20.5% vs. 21.6%), whereas symptomatic examinees had higher rates in the youngest strata. In exploratory cross-sectional analyses within the 40–44 group, total cholesterol (odds ratio, OR = 1.47) and body mass index (BMI) (OR = 1.05) showed associations with adenoma, without establishing causality, with BMI elevation conferring risk only in women (p for interaction = 0.018). Conclusions: Adenoma risk accelerates at 33 and high-risk lesions escalate at 39, providing age-stratified risk benchmarks for adults under 45 in a predominantly symptomatic Chinese cohort. These inflection points warrant prospective validation in asymptomatic screening populations. Full article

Colorectal cancer (CRC) remains a major global health burden, and early detection through population-based screening programs significantly reduces both incidence and mortality. Although gut microbiome-based biomarkers have emerged as promising non-invasive tools for CRC detection, limited evidence is available regarding patient acceptance and compliance with microbiome-based screening studies, factors that may influence their future implementation in clinical practice. We conducted a preliminary analysis of an ongoing multicenter, prospective observational study designed to develop a gut microbiome-based diagnostic tool for CRC and advanced colorectal adenomas in fecal immunochemical test (FIT)-positive individuals. The primary objective of this preliminary analysis was to evaluate patient acceptance and compliance with participation in a microbiome-based study within an organized CRC screening setting. Secondary objectives included describing the clinical, endoscopic, and histopathological characteristics of the enrolled cohort. FIT-positive individuals referred for screening colonoscopy at participating Italian centers were screened for eligibility, underwent colonoscopy, and were invited to provide a stool sample for microbiome analysis. A total of 315 individuals were screened, of whom 212 (67%) were enrolled. Among eligible patients, 90% agreed to enroll after receiving study information. Overall, 200 (94%) of enrolled individuals completed the required study activities, including stool sample collection and colonoscopy, indicating high compliance with study procedures. Colonoscopy was performed in 209 patients (99% of enrolled patients). CRC was detected in 7 patients (3%), and advanced colorectal adenomas in 39 (18%), while 86 (41%) colonoscopies were negative. The positive predictive value of FIT was 3.35% for CRC and 18.66% for advanced adenomas. In our preliminary analysis, patient acceptance and compliance with microbiome-based sampling were high among FIT-positive individuals undergoing CRC screening. These findings support the feasibility of conducting microbiome-based studies within organized screening programs. Analyses aimed at developing and validating the microbiome-based diagnostic tool are currently ongoing and are beyond the scope of the present report. Full article

Background/Objectives: Colorectal cancer commonly develops through an adenoma–carcinoma sequence, but the immune alterations accompanying this transition remain incompletely understood. Because we previously observed reduced γδ T cells, increased apoptosis, and frequent microsporidia infection in colorectal cancer, we investigated whether similar changes are already present in colonic adenomas. Methods: We studied 55 subjects, including 30 patients with colonic adenomas, 10 with colorectal cancer, and 15 healthy controls. Peripheral blood T-cell subsets and apoptosis were assessed by flow cytometry, tissue expression of IL-7, CD127, and CD132 was analyzed by RT-PCR, and microsporidia were detected in colonic tissues by immunofluorescence and real-time PCR. Results: γδ T cells were progressively reduced in colonic adenomas and further decreased in colorectal cancer, while apoptosis of both αβ and γδ T cells increased compared with healthy subjects. Tissue expression of CD132 was significantly downregulated in adenomas and colorectal cancer, whereas IL-7 expression was increased, particularly in adenomatous tissue, consistent with a compensatory mechanism attempting to preserve T-cell homeostasis despite reduced CD132 expression. Microsporidia prevalence rose from healthy controls to patients with colonic adenomas and colorectal cancer, and CD132 expression was more markedly reduced in microsporidia-positive colonic adenoma and cancer tissues. Conclusions: These findings indicate that altered IL-2 receptor-related signaling, γδ T-cell depletion, and increased apoptosis are already present at the adenoma stage and are associated with microsporidial infection. This pattern suggests a potential link between parasitic colonization and local immune dysfunction during colorectal tumorigenesis. Full article